Synthesis and Bioactivity Assessment of Novel Quinolinone-Triazole Hybrids

Click chemistry, and particularly the Cu-catalyzed Azide Alkyne Cycloaddition (CuAAC) reaction has gained increased attention in recent years as an invaluable tool for synthesizing pharmaceutical active organic compounds. In this study, quinolinones and triazoles, two bioactive heterocyclic moieties amenable to various substitutions, were employed to design and synthesize novel quinolinone-triazole hybrid molecules via the CuAAC click reaction under microwave irradiation. The synthesized hybrid molecules and their alkyne precursors were structurally characterized and evaluated for their antioxidant capacity, lipoxygenase (LOX) inhibitory activity, cell viability using HaCaT epithelial cells, and cytotoxicity against two cancer lines. The results indicated that, among the precursors, alkyne 4c exhibits the best combined antioxidant and anti-inflammatory activity (100% lipid peroxidation inhibition, IC₅₀ = 22.5 μM for LOX inhibition); among the hybrid molecules, compound 5a was the most potent (98.0% lipid peroxidation inhibition, IC₅₀ = 10.0 μM for LOX inhibition). Regarding the assessment of HaCaT cell viability, all studied compounds showed encouraging results, with cell viability rates between 61.5% and 100%. Moreover, based on the results of the cytotoxicity against cancer lines A549 and A375, it emerged that the tested compounds exhibited moderate-low or no cytotoxicity. These results highlight the potential of quinolinone-triazole hybrids as valuable candidates in drug discovery.